Considerable progress has been made on the structure and expression of the crystallin genes of the lens. The entire 25 kb locus comprising the 2 Delta-crystallin genes and the Beta35 and Beta19/26 cDNAs of the chicken have been sequenced. The Delta-crystallin genes are remarkably similar, with each containing 17 exons and encoding proteins with 91% sequence identity. Surprisingly, however, the 48K and 50K Delta-crystallin polypeptides could both be derived in experiments using a cloned Delta1 cDNA. The promoter regions of the 2 Delta genes are very similar and GC-rich, although a CAAT box is present only in the Delta1 promoter. The chicken Beta35 was found to be homologous to the mammalian BetaB1; both have the characteristic N-terminal, alternating pro-ala sequence. The human and chicken AlphaA-crystallin gene have been isolated; the chicken gene has been fully sequenced and the human gene partially sequenced. The murine AlphaA-crystallin gene has been mapped to chromosome 17. Functional studies have shown that the Delta1 gene promoter is more active than the Delta2 promoter in a Hela cell extract and in its ability to drive the bacterial chloramphenicol acetyltransferase (CAT) gene in transfected cultured lens cells. Competition experiments indicate that the Delta1 promoter utilizes Sp1 as a transcription factor in a Hela cell extract. The AlphaA-crystallin promoter was shown to be extremely tissue-specific both in cultured cells and in transgenic mice. Analysis of the murine AlphaA-crystallin promoter suggested the existence of several elements, including an upstream enhancer-like sequence required for in vivo expression.